This program project consists of four distinct but conceptually linked research projects focusing on the mechanisms of emergence of several different zoonotic viruses. Each project includes both field and laboratory studies. The first Project will examine the pathogenesis and transmission of two newly recognized hantaviruses (Black Creek Canal and Cano Delgadito) in their natural cotton rat hosts, Sigmodon hispidus and S. alstoni, respectively. This work will be done in collaboration with scientists at the Centers for Disease Control and Prevention (CDC) in Atlanta, utilizing the maximum containment facilities of the Special Pathogens Branch. Field studies will also be done to determine the prevalence of Cano Delgadito infection among rodents and people living in a rural area where this hantavirus occurs. The second Project will examine the genetic and phenotypic changes leading to the emergence of epidemic/epizootic strains of Venezuelan equine encephalitis (VEE) virus. Field studies will be done at several enzootic foci of VEE - ID virus activity in Venezuela and Colombia. Reverse genetic approaches will be used in the laboratory to study VEE virulence determinants. The third Project will study the changing epidemiology of Oropouche fever, a midge-borne viral disease that is often confused with dengue. Epidemiologic and entomologic studies will be done in an Oropouche virus-endemic region near Iquitos, Peru, in collaboration with scientists at the U.S. Naval Medical Research Institute Detachment in Lima. Laboratory work on this project will include molecular phylogenetic studies of ORO-like viruses from a variety of localities and sources in South America and Panama, the development of specific recombinant antigens for use in serologic diagnosis of the disease, and investigation of the etiology of the recurrent illness frequently associated with ORO fever. The fourth Project will develop a model for mapping the location and distribution of enzootic foci and sites of emergence potential for VEE virus in Venezuela, utilizing satellite imagery, computerized geographic information systems and ground observations. The latter project is submitted for consideration for funding by NASA in conjunction with NIAID support. Although the projects involve different viruses, they are thematically unified in addressing how zoonotic viruses are transmitted and maintained in nature and how they emerge to become significant human pathogens. Data resulting from the research will enhance prediction, prevention and control of several emerging viral diseases occurring in the Americas.